Coronary angiography is used to identify and measure the luminal dimensions of blood vessels. Angiography however, cannot provide information about plaque content.
The subject invention addresses this deficiency by placing an imaging detector into the arteries to detect and characterize early-stage, unstable coronary artery plaques. This can provide a signature relevant to the 70% of heart attacks that are caused by minimally obstructive, unstable plaques that are too small to be detected by angiography.
The present invention describes construction of an intravascular imaging detector which works in concert with systemically administered plaque-binding beta-emitting radiopharmaceuticals such as 18-Fluorodeoxyglucose (18-FDG). The apparatus of the present invention accomplishes these benefits by identifying and localizing these plaque-binding beta or conversion electron emitting radiopharmaceuticals.
Intravascular imaging probes constructed in accordance with the principles of the present invention yield detectors, which satisfy the difficult constraints of the application in terms of size of the device, needed sensitivity, and conformance to the intravascular requirements.
The apparatus of the present invention will allow new targeted and cost effective therapies to prevent acute coronary artery diseases such as: unstable angina, acute myocardial infarction, and sudden cardiac death.
The present invention generally provides an apparatus for intravascular imaging to detect and characterize early-stage, vulnerable coronary artery plaques. The detector works by identifying and localizing plaque-binding beta-emitting radiopharmaceuticals.
The apparatus of the present invention includes a radiation detector(s) with a predetermined intrinsic spatial resolution, typically between 1-8 mm, and preferably between 1-3 mm. In some embodiments, the detector is in the form of a detector array. The detector array can include a plurality of detector units or pixels built onto a single chip or separate chips. The detector(s) are typically integrated into an intravascular catheter so that it can be manipulated through the body lumen, optionally using a guidewire in much the same way as a balloon catheter for angioplasty.
Optionally, the detectors of the present invention can be embedded within a balloon or other expansible structure such as a flexible membrane, which is collapsed or deflated during guidance through the body lumen. The structure can then be deployed at a target site so that the detector is pressed up against the inside of the artery wall bringing the detector in contact with the plaque. This optimizes the particle to gamma and signal to background ratios for charged particle imaging.
During transit through the artery, software or other analyzing means may decode the data obtained by the detector to operate in a search mode. The search mode is typically performed by summing all of the pixels of the detectors to obtain a fast gross count. Once a threshold gross count is detected (e.g. a high count rate region is localized), the software can switch to an imaging mode to produce a higher resolution image to provide more detail of the plaque. For embodiments using a balloon, the balloon can be kept in a deflated configuration during the fast gross count and the balloon can be inflated when the detectors are switched to the imaging mode.
Exemplary radiation detectors include: 1) Scintillators; 2) Imaging plates; 3) Semiconductors; and 4) Ionization chambers. Each of the described embodiments yields a detector which satisfies the difficult constraints of the application in terms of size of the device, needed sensitivity, and conformance to the intravascular requirements.
The apparatus of the present invention preferably provides both high beta particle detection efficiency and sufficient sensitivity in the very small detector volume afforded by an intravascular or other medical catheter tip.
Monte Carlo simulations developed for tracking beta trajectories and deposited energy have been used to guide the choice of material and shape and size of the pixel elements. Whereas the volume of the detector is limited by the arterial lumen, the correct pixel dimensions (laterally) are comparable with the beta range (in the specific detector). Monte Carlo simulations have been performed for F-18 positrons and T1-204. The simulations have been used as a basis for the detector design.
The sensitivity has also been directly measured for beta particles for each of the fabricated prototype detectors. This has been done with T1-204 and F-18 beta emitters.
The apparatus of the present invention allows for high efficiency for betas and very low detection efficiency for 511 keV gammas. Generally we have precluded materials that have either high atomic number or high density Gasses, liquids, light plastics and thin low-Z semiconductors have been found to be preferable in this respect to high Z compound semiconductors.
The sensitivity and immunity to gamma background is confirmed with the use of filter paper disks containing known F-18 source activity. A series of measurements is taken from which mean and standard deviation counts per second is calculated. A second series of the measurements is taken in the same configuration with exception that a 0.2 mm thick piece of stainless steel is placed in front of detector face this time. By dividing the results from the first set of measurements by the amount of the activity on the disk, the combined (beta and photon) sensitivity is calculated. The beta sensitivity is calculated by subtracting the pure photon rate from the combined count rate. The results are analyzed versus energy thresholds ranging from the noise level up to 495 keV (Compton edge for 511 keV).
The apparatus of the present invention allows the device to be operated in such a way as to allow the detector to be pressed up against the inside of the artery wall. Three of the described embodiments: the gas scintillator, the semiconductor detector and the ionization chamber detector are designed to be embedded within a balloon or other expansible structure which although deflated during guidance through the artery or other body lumen, can be inflated when at a plaque site. The balloon can be alternatively deflated during transit through the artery and then inflated when at a suspicious suite. In addition the detector has the ability to operate in a search mode by summing all of the pixel responses to obtain a fast gross count during transit through the artery. The apparatus is switched to an “imaging” mode to obtain high-resolution detail of the plaque when a high-count rate region is localized.
The apparatus of the present invention allows for spatial resolution on the order of 1 mm, which is sufficient to interrogate a plaque. This also is of the same order as the beta range. The spatial resolution is confirmed by measurement of the point spread function and the inter-element cross talk of the imager to beta particles.
The apparatus of the present invention allows construction to maximize its passive properties, which are attractive due to the higher degree of safety during procedures. The preference had been given to detectors composed of inert materials due to the higher degree of safety during procedures.
The detection mechanisms of the apparatus of the present invention allow for the highest signal and sensitivity of the detector. This criterion favors the semiconductor detector approach, which offers the most efficient energy transfer.
The apparatus of the present invention allows for a construction that can be integrated with the catheter and guidewire.